Bacterial and Human Biomarkers of Prognostic Value for Severe Legionnaire's Disease (Proglegio)

Legionnaires' disease (LD) is a relatively common pneumonia in France (1200 cases/year), 98% of cases are hospitalized and 40% require intensive care unit (ICU) admission. Risk factors that may predispose to acquisition of LD are well known. Some studies suggest that genetic factor may also enhance susceptibility to LD.

The mortality rate remains high (10% to 33% in ICUs) despite improved diagnostic and therapeutic management of patients. Few prospective studies have assessed the factors associated with LD outcomes, particularly death, and most of them involved a limited number of patients.

In a multicentre cohort study, the investigators recently identified risk factors associated with higher mortality such as female sex, age, ICU stay, renal failure, corticosteroid treatment and enhanced pro-inflammatory status, as assessed by higher C-reactive protein level (PMID: 22005914). Other factors are suspected but their involvement has not been formally demonstrated including a high infectious bacterial load, particular virulence of Legionella strain, and an in vivo selection of mutants resistant to prescribed antibiotics. Disease progression is highly variable from one patient to another, and usually remains unpredictable. There are no objective criteria to predict the prognosis of these patients.

The clinical course of patients with LD remains difficult to predict because no predictive biomarkers have yet been characterized and the demonstration of the presence of mutants to antibiotics in vivo has never been done.

The main objective of the study is to correlate the L. pneumophila load (detected by PCR) to the clinical outcome of the LD infection. Clinical severity will measured by the SOFA score (Sepsis -Related Organ Failure Assessment) or the PELOD score (Pediatric Logistic Organ Dysfunction).

Secondary objectives are to identify new host and bacterial biomarkers associated with poor outcome of LD.

Study Overview

• Status: Recruiting
• Conditions: Legionella
• Intervention / Treatment: Other: Skin biopsy for genetic analyze

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gérard LINA, MD PhD; Phone Number: +33 4 78 86 44 93; Email: gerard.lina@chu-lyon.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • CHU Amiens
    • Contact: Claire ANDREJAK
    • Principal Investigator: Claire ANDREJAK
  • Angoulême, France
    • Recruiting
    • CHU d'Angouleme
    • Contact: David SCHNELL
    • Principal Investigator: David SCHNELL
  • Besançon, France
    • Recruiting
    • CHRU Besançon
    • Contact: Gilles Capellier
    • Principal Investigator: Gilles CAPELLIER
    • Sub-Investigator: Jean-Christophe NAVELLOU
  • Brest, France
    • Recruiting
    • CHU Brest
    • Sub-Investigator: Rozenn LE BERRE
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Contact: Jean Pierre Quenot
  • Grenoble, France
    • Recruiting
    • CHU Grenoble
    • Principal Investigator: Carole SCHWEBEL
    • Contact: Carole SCHWEBEL
  • Lille, France
    • Recruiting
    • CHU Lille
    • Contact: Nseir SAADALLAH
    • Principal Investigator: Nseir SAADALLAH
  • Lyon, France, 69000
    • Recruiting
    • Hôpital Edouard Hériot
    • Principal Investigator: Laurent ARGAUD
    • Contact: Laurent ARGAUD
  • Lyon, France, 69000
    • Recruiting
    • Hopital de La Croix Rousse
    • Contact: Jean-Christophe RICHARD
    • Principal Investigator: Jean-Christophe RICHARD
    • Principal Investigator: Vanessa LABEYE
    • Principal Investigator: Yvan Jamilloux
    • Principal Investigator: Oriane PELTON
  • Nantes, France
    • Recruiting
    • CHU de Nantes
    • Contact: François-Xavier BLANC
  • Paris, France, 75020
    • Recruiting
    • Hopital Tenon
    • Principal Investigator: Muriel FARTOUKH
  • Paris, France, 75010
    • Recruiting
    • Hôpital Saint Louis - APHP
    • Contact: Virginie LEMIALE, MD
    • Principal Investigator: Virginie LEMIALE, MD
  • Paris, France
    • Recruiting
    • APHP Hôpital Bichat
    • Contact: Jean Francois TIMSIT
    • Principal Investigator: Jean Francois TIMSIT
  • Pierre-Bénite, France
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Principal Investigator: Nathalie FREYMOND
    • Sub-Investigator: Pierre-jean SOUQUET
  • Rennes, France
    • Recruiting
    • Chu Rennes
    • Contact: Arnaud Gacouin
  • Saint-Étienne, France, 42000
    • Recruiting
    • CHU Saint Etienne
    • Contact: Frederic LUCHT
    • Principal Investigator: Frederic LUCHT
    • Principal Investigator: Sophie PERINEL RAGEY
  • Strasbourg, France
    • Recruiting
    • CHU Strasbourg Nouvel Hôpital Civil
    • Contact: Ferhat MEZIANI
  • Tourcoing, France
    • Recruiting
    • CH Gustave Dron
    • Contact: Serge ALFANDARI
    • Principal Investigator: Serge ALFANDARI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with medical and biological signs of legionnaires' disease.
• Pediatric patients regardless of age but with a minimum weight of 7.5 kg with medical and biological signs of legionnaires' disease.
• Patient and/or his/her legal representative have reviewed the patient information/informed consent form and have given written informed consent.

Exclusion Criteria:

• None Legionella pneumophila Legionnaires' disease.
• Patients for whom respiratory secretions can't be obtained.
• Cases diagnosed only by serology.
• Outpatients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: This study is a non-drug one arm study; Skin biopsy for genetic analyze

Other: Skin biopsy for genetic analyze; It will be offered to a subgroup of adult patients carrying genetic markers predisposing to the severity of the LD infection, a skin biopsy in order to realize genetic analyses. This visit will be conducted once the results of genetic markers obtained (between 30 and 36 months), a specific consent will be required to patients. The skin biopsy will be performed according to the Clinical Department use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Legionnaire's disease severity measured by SOFA/PELOD score	No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection	At Hospital Output, on average 1 Day
Bacterial load measured by PCR	No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection	At Hospital Output, on average 1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific cytokine profile	Cytokine profile will be measured at local level (pulmonary) and/ or systemic level (serum) and associated with severity	Up to Day 5
Genomic analyzes	Genomic analyzes of bacterial genes will be associated with the legionella severity	At inclusion, up to 48 hours
Pulmonary microbiota	Metagenomic approaches and NGS will be used to associate a specific microbiota, or changes in the severity of LD infection	At inclusion, up to 48 hours

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Study Chair: Gérard LINA, Hospices Civils of Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 23, 2017
• Primary Completion (ANTICIPATED): January 31, 2024
• Study Completion (ANTICIPATED): January 31, 2025

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: February 21, 2017
• First Posted (ACTUAL): February 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Legionnaires' Disease; Legionellosis
• Other Study ID Numbers: 69HCL16_0131

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No